Zealand Pharma announced topline results on October 7, 2026 from ZUPREME-2, a Phase 2b trial testing its amylin analog petrelintide in adults with overweight or obesity who also have type 2 diabetes. The company said the trial met its primary endpoint, adding a second positive readout for petrelintide after the ZUPREME-1 trial in people without diabetes.
What the ZUPREME-2 Trial Tested
ZUPREME-2 was a randomized, double-blind, placebo-controlled, U.S.-based trial that enrolled 220 adults with overweight or obesity and type 2 diabetes who were already taking metformin, with or without an SGLT2 inhibitor. Participants had a mean baseline body mass index of 36.3 and a mean baseline A1C of 8.0%, and all were counseled on a reduced-calorie diet and increased physical activity alongside their assigned treatment. The trial tested three once-weekly doses of petrelintide, a long-acting synthetic analog of human amylin given by subcutaneous injection, with dose escalation over as long as 16 weeks. The primary endpoint was assessed at week 28, with safety follow-up continuing to week 38.
Weight Loss and Blood Sugar Results
At week 28, participants on petrelintide lost a mean of 7.4% to 9.2% of their body weight, depending on dose, compared with 2.0% on placebo, based on the trial's efficacy estimand (results under the alternative treatment-regimen estimand were largely similar). On the glycemic side, A1C fell by as much as 0.65 percentage points on petrelintide, versus a 0.23-point increase on placebo — a placebo-adjusted difference of roughly 0.6 to 0.9 percentage points across the dose groups.
Safety and Tolerability
Zealand reported no unexpected safety signals. Most adverse events were gastrointestinal, generally mild, and concentrated during the dose-escalation period. Discontinuations specifically due to GI side effects were low and similar between groups: 1.9% on petrelintide versus 1.7% on placebo. The company said this tolerability profile was consistent with what was seen in ZUPREME-1, an earlier 42-week Phase 2 trial of petrelintide in people without type 2 diabetes.
How Petrelintide Differs From GLP-1 Drugs
Petrelintide isn't a GLP-1 receptor agonist like semaglutide or tirzepatide. It's an analog of amylin, a separate hormone that the pancreas co-secretes with insulin and that acts on different brain pathways to influence satiety and gastric emptying. Zealand and other companies, including Novo Nordisk with cagrilintide, are betting that amylin-pathway drugs can produce meaningful weight loss on their own or add to the effect of GLP-1 drugs when combined, though combination data for petrelintide specifically is still early.
What Comes Next
Zealand said it has already dosed the first participants in a Phase 3a program developed with partner Roche, consisting of three trials — ZUPREME-3, ZUPREME-4, and ZUPREME-5 — expected to enroll roughly 7,000 people combined. Separately, the companies are planning a Phase 2 trial pairing petrelintide with Roche's GLP-1 candidate enicepatide (CT-388) in the second half of 2026. Zealand's chief medical officer, David Kendall, said the ZUPREME-2 results "further support the potential of petrelintide in chronic weight management," and the company said fuller data from the trial will be presented at an upcoming scientific conference.
Regulatory Status
Petrelintide remains an investigational drug. It is not approved by the FDA or any other regulator for any use, and the results described here come from a company announcement of topline findings rather than a peer-reviewed publication, which typically follows later with more complete data and independent scrutiny. Readers who are weighing weight-loss or diabetes treatment options today should discuss currently approved therapies with a licensed physician rather than treat an investigational drug's trial results as a basis for treatment decisions.